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. 2021 Oct 19;37(3):109875.
doi: 10.1016/j.celrep.2021.109875.

A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis

Toshinori Nakagawa  1 , David J Jörg  2 , Hitomi Watanabe  3 , Seiya Mizuno  4 , Seungmin Han  5 , Tatsuro Ikeda  6 , Yoshiki Omatsu  7 , Keiko Nishimura  6 , Miyako Fujita  6 , Satoru Takahashi  8 , Gen Kondoh  3 , Benjamin D Simons  9 , Shosei Yoshida  10 , Takashi Nagasawa  11
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Free article

A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis

Toshinori Nakagawa et al. Cell Rep. .
Free article

Abstract

In mouse testis, a heterogeneous population of undifferentiated spermatogonia (Aundiff) harbors spermatogenic stem cell (SSC) potential. Although GFRα1+ Aundiff maintains the self-renewing pool in homeostasis, the functional basis of heterogeneity and the implications for their dynamics remain unresolved. Here, through quantitative lineage tracing of SSC subpopulations, we show that an ensemble of heterogeneous states of SSCs supports homeostatic, persistent spermatogenesis. Such heterogeneity is maintained robustly through stochastic interconversion of SSCs between a renewal-biased Plvap+/GFRα1+ state and a differentiation-primed Sox3+/GFRα1+ state. In this framework, stem cell commitment occurs not directly but gradually through entry into licensed but uncommitted states. Further, Plvap+/GFRα1+ cells divide slowly, in synchrony with the seminiferous epithelial cycle, while Sox3+/GFRα1+ cells divide much faster. Such differential cell-cycle dynamics reduces mitotic load, and thereby the potential to acquire harmful de novo mutations of the self-renewing pool, while keeping the SSC density high over the testicular open niche.

Keywords: Plvap; Sox3; lineage tracing; mice; spermatogenic stem cells; stem cell heterogeneity; testis; tissue homeostasis.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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